1. Field of the Invention
The invention generally relates to a multivalent anthelminthic vaccine that targets both hookworm and schistosomiasis. In particular, the invention provides a vaccine that includes at least two hookworm antigens, of which one is a third-stage larval stage antigen and one is an adult stage antigen, and at least one schistosome antigen. In some cases, full or partial sequences of schistosome antigens may be fused with full or partial sequences of hookworm (Necator americanus) to produce recombinant chimeric antigens.
2. Background of the Invention
Hookworm infection and schistosomiasis are the two most important parasitic helminth infections of humans. Together these two helminthiases are responsible for an estimated 345,000 deaths and 26.6 million disability adjusted life years (DALYs) annually making them second only to malaria as the most important causes of human parasitic infection (Table 1).
TABLE 1Disease burden of hookworm and schistosomiasis and comparison with malariaDALYsMajor(DisabilityMajor clinicalGlobalGeographicadjusted lifefeatures andDiseasePrevalenceRegionsDeathsyears)disabilitiesHookworm Infection576 millionSub-Saharan65,00022.1 millionAnemia, physical &(Major species:Africa, SEcognitive retardationNecator americanus;Asia, BrazilMinor species:Ancylostoma duodenale)Schistosomiasis207 millionSub-Saharan280,000 4.5 millionAnemia, liver disease,(Major species:Africa, Brazilurogenital disease andSchistosoma mansonia andphysical & cognitiveSchistosoma haematobium;retardationMinor species:Schistosoma japonicum)Hookworm andSub-Saharan345,00026.6 millionSchistosomiasisAfrica, BrazilMalaria300-500Sub-Saharan1,200,00046.5 millionAnemia, cerebralmillionAfricamalaria, AcuteRespiratory DistressSyndrome (ARDS)
Both hookworm and schistosomiasis are co-endemic in many regions of the world. In both sub-Saharan Africa and Brazil these two helminth infections not only exhibit a high degree of geographic overlap, but there is evidence that co-infections with hookworm and schistosomes are extremely common, and there is evidence that hookworm promotes susceptibility to schistosomiasis (Fleming et al, 2006; Raso et al, 2007). The co-morbid effects of hookworm and schistosomiasis are profound and include severe anemia and physical and intellectual growth retardation in children, as well as adverse pregnancy outcome (Hotez and Ferris, 2006; Hotez et al, 2006). There is additional evidence that both hookworm and schistosomiasis increase susceptibility and worsen the severity of malaria and HIV/AIDS (Hotez et al, 2006; 2007).